The present invention relates to novel pharmaceutical compositions containing as the active ingredient the compound 5-methyl-1-phenyl-2-(1H)-pyridone (AMR-69) having the formula
Certain substituted pyridones and particularly those wherein the N-substituents are phenylamine derivatives are known to possess analgesic qualities. Several of the latter are disclosed in British Patent No. 1,238,959 and U.S. Pats. Nos. 2,947,754 and 2,947,755. None of these compounds, during the intervening years have exhibited sufficient potency and/or safety to provide commercially acceptable therapeutic compositions.
A number of alkyl substituted pyridones have been illustrated in the Examples of U.S. Pats. Nos. 3,644,626 and 3,655,897. The examples given in these patents and the patents cited above would seem to teach that the most effective pyridones would be those having an aminophenyl N-substituent or those having an alkyl substituent but no N-substituent. There is no indication given that a composition having the structure of the present invention with the methyl and phenyl radicals assuming, respectively, the 5 and 1 positions, on the pyridone ring would give the enhanced therapeutic properties and concomitant low toxicity as set forth below.
Pyridones such as those described above have generally been prepared either by ring closure of the appropriate diol intermediates (U.S. Pat. No. 2,947,754) which are expensive when available; by the reaction of cyanoacetanilide with 2, 4-diketones (Chem. Abst. 72, 308); by the catalytic dehydrogenation of the appropriate dihydro2-pyridone (J. Org. Chem. 26, 2586) or by the reaction of an appropriate 2-(1H)-pyridone alkali metal salt (which is prepared by reaction of the pyridone with an alkali metal hydride) with the appropriate halogenated aryl compound in overall yields of about 15-25% (British Patent No. 1,238,959, page 9) (U.S. Pat. No. 2,947,755) As will be apparent to those skilled in the art, these processes are difficult, uneconomical and often result in poor yields after extended manipulation of expensive starting materials.
While 5-methyl-1-phenyl-2-(1H)-pyridone has been used as a starting material and as an intermediate in the synthesis of various pyridones reported to have therapeutic properties, there is no disclosure that this specific pyridone itself would have effective therapeutic properties in treating subjects having a wide range of symptoms.